Researchers of the group Neuropharmacology and Pain of Bellvitge Biomedical Research Institute (IDIBELL), the University of Barcelona (UB) and Esteve, have developed a technology that enables to determine drugs' analgesic potential before being tested in animal models. The finding saves time and money in the research on new effective pain treatments.

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Traditionally in the development of analgesic drugs, the effectiveness of these molecules has been proved by using pain animal models, a hard, expensive and unclear process from a pharmacological point of view. Therefore, the great challenge is to develop more effective methodologies. Francisco Ciruela, senior lecturer of the Department of Pathology and Experimental Therapy at UB and researcher of the Group Neuropharmacology and Pain, explains: “We are talking about thousands of drugs; so, before testing them in preclinical pain models, that is, animal models, it will be useful to assess their antinociceptive potential and select the ones that show low effectiveness”.

The study led by Ciruela describes a new technology to establish the analgesic activity of durgs before being tested in animal models. “We have developed a Receptor Fluorescence Resonance Energy Transfer (FRET) based biosensor that allow us to classify in a simple system (cell culture) sigma-1 receptor ligands into agonist and antagonists”, details the researcher.

The experiments carried out by Esteve and the research group led by Dr Ciruela (IDEBELL-UB) with known drugs established a direct correlation between the FRET change promoted by drugs and their analgesic effect in a pain animal model. Results show that, whereas sigma-1 agonists reduce FRET signal and have low analgesic effects, sigma-1 antagonists increase FRET signal and have high analgesic effects in pain animal models.

“Thanks to this well-defined pattern —explains Dr Ciruela—, we can predict the analgesic behaviour of a molecule”. Therefore, if FRET signal is reduced —that is, if it is an agonist—, it won’t have analgesic effects on the pain animal model; however, if FRET signal is increased —in other words, if it is an antagonist—, it will have maximum analgesic effects and, therefore, it will be a suitable candidate to be tested in vivo.

The researcher points out that the new technology has already been patented, and “although is too early to get the most of it —because FRET measures are now done one drug by one—, it is expected that it will be soon applied in an extensive way to the development of sigma-1 receptor antagonist analgesic drugs”, highlights Ciruela. Therefore, the system will be robotized in order to develop a tool technically known as ‘high-throughput screening’ (HTS), in other words a method to test many medicines in a quick and effective manner.

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